Cyclopropanecarbonyl chloride → 2-Chloro-4-fluoro-N-(3-(N-cyclopropylcarbonyl-N-(1-methylpiperidin-4-yl)amino)phenyl)benzamide hydrochloride

HRID 1716909Notes

Reaction equation

HRID 1716909 reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:5]=1[C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH:16]2[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]2)[CH:10]=1)=[O:7].[CH:28]1([C:31](Cl)=[O:32])[CH2:30][CH2:29]1>O1CCOCC1>[ClH:3].[Cl:3][C:4]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:5]=1[C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N:15]([C:31]([CH:28]2[CH2:30][CH2:29]2)=[O:32])[CH:16]2[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]2)[CH:10]=1)=[O:7]

Participants

4

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 112127052-Chloro-4-fluoro-N-(3-(1-methylpiperidin-4-ylamino)phenyl)benzamide dihydrochloride

Product 1

HCID 669391632-Chloro-4-fluoro-N-(3-(N-cyclopropylcarbonyl-N-(1-methylpiperidin-4-yl)amino)phenyl)benzamide hydrochlorideYield 172.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
106 °C

Procedure

Combine 2-chloro-4-fluoro-N-(3-(1-methylpiperidin-4-ylamino)phenyl)benzamide dihydrochloride (Example 1, 48 mg, 0.134 mmol), dioxane (1 mL) and cyclopropylcarbonyl chloride (0.013 mL, 0.148 mmol). Shake and heat (106° C.) in a J-Kem® Reaction Block for 2 hr. Load onto a SCX column (Varian) and elute with 2 M ammonia methanol to give the free base of the title compound (54 mg, 93%). Following a salt formation method similar to that described in Example 1 gives the title compound as a white solid (47 mg): mp 133-6° C.; mass spectrum (freebase, ion spray): m/z=430.1 (M+1), 1H NMR (freebase, CDCl3): 8.31 (bs, N—H), 7.76 (dd, J=6.0 Hz, 8.6 Hz, 1H), 7.61-7.56 (m, 2H), 7.38 (t, J=8.0 Hz, 1H), 7.19 (dd, J=2.4 Hz, 8.3 Hz, 1H), 7.09 (td, J=2.4 Hz, 8.2 Hz, 1H), 6.96 (d, J=8.2 Hz, 1H), 4.62-4.53 (m, 1H), 2.80 (bd, J=11.5 Hz, 2H), 2.20 (s, 3H), 2.05 (td, J=2.2 Hz, 12.1 Hz, 2H), 1.83-1.69 (bm, 2H), 1.59-1.37 (bm, 2H), 1.21-1.13 (m, 1H), 0.99-0.89 (bm, 2H), 0.56 (bd, J=7.4 Hz, 2H). Analysis calc'd for C23H26Cl2FN3O2.0.8H2O: C, 57.46; H, 5.79; N, 8.74. Found: C, 57.16; H, 5.73; N, 8.70.

Workup

  1. customin a J-Kem® Reaction Block for 2 hr
  2. washLoad onto a SCX column (Varian) and elute with 2 M ammonia methanol

Sources & evidence

ORD record
ord-b76f5a4453f14ed3ace3778039e9d13a
Source dataset
uspto-grants-2010_09
Patent number
US07803813B2

Reaction notes

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